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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2014

Open Access 01-12-2014 | Research

Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation

Authors: Shuang Wu, Wenjun Yu, Xiaoyan Qu, Rong Wang, Ji Xu, Qiguo Zhang, Jiaren Xu, Jianyong Li, Lijuan Chen

Published in: Journal of Hematology & Oncology | Issue 1/2014

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Abstract

Background

Dysregulated microRNA (miRNA) expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core component of the RNA-induced silencing complex (RISC), can directly bind to miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study showed that AGO2 knockdown suppressed human umbilical vein endothelial cell (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this study was to characterize these roles and effects and their associated mechanisms.

Results

Supernatants from AGO2-overexpressing MM lines induced HUVEC migration and accelerated tube formation. Conversely, supernatants from AGO2-knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover, a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2 could drive neovessel formation in MM lines in vivo. Using an miRNA microarray, we observed that 25 miRNAs were upregulated and 7 were downregulated in response to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2 whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively regulated by AGO2.

Conclusions

We conclude that AGO2 can drive neovessel formation in vitro and in vivo by dysregulating the expression of some angiogenic miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster, along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated angiogenesis by targeting angiogenesis-related genes.
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Metadata
Title
Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation
Authors
Shuang Wu
Wenjun Yu
Xiaoyan Qu
Rong Wang
Ji Xu
Qiguo Zhang
Jiaren Xu
Jianyong Li
Lijuan Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-7-40

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